Reevaluation of SNP heritability in complex human traits
File(s)Speed-assume.doc (520 KB)
Accepted version
Author(s)
Speed, D
Cai, N
Johnson, MR
Nejentsev, S
Balding, DJ
Type
Journal Article
Abstract
SNP heritability, the proportion of phenotypic variance explained by SNPs, has been reported for many hundreds of traits. Its estimation requires strong prior assumptions about the distribution of heritability across the genome, but current assumptions have not been thoroughly tested. By analyzing imputed data for a large number of human traits, we empirically derive a model that more accurately describes how heritability varies with minor allele frequency (MAF), linkage disequilibrium (LD) and genotype certainty. Across 19 traits, our improved model leads to estimates of common SNP heritability on average 43% (s.d. 3%) higher than those obtained from the widely used software GCTA and 25% (s.d. 2%) higher than those from the recently proposed extension GCTA-LDMS. Previously, DNase I hypersensitivity sites were reported to explain 79% of SNP heritability; using our improved heritability model, their estimated contribution is only 24%.
Date Issued
2017-05-22
Date Acceptance
2017-04-18
Citation
Nature Genetics, 2017, 49 (7), pp.986-992
ISSN
1061-4036
Publisher
Nature Publishing Group
Start Page
986
End Page
992
Journal / Book Title
Nature Genetics
Volume
49
Issue
7
Copyright Statement
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000404253300006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
RDA03
RD610
P35076
RDA03
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENOME-WIDE ASSOCIATION
RESTRICTED MAXIMUM-LIKELIHOOD
MISSING HERITABILITY
MIXED-MODEL
COMMON SNPS
PARTITIONING HERITABILITY
RHEUMATOID-ARTHRITIS
GENETIC ARCHITECTURE
HUMAN HEIGHT
VARIANTS
Publication Status
Published